This request is for funds to purchase a multi-photon Leica TCS SP5 fluorescence scanning confocal microscope. This will be a dedicated core equipment for the formally established Multi-Photon Core at the USC Keck School of Medicine in the Health Sciences Campus. The core is an integral part of, and funded by the USC Biomedical Imaging Science Initiative (BISI). The mandate of this new core facility is to provide access to multi- photon in vivo imaging of intact organs in small animals which is a long-desired, but still missing service on campus. This state-of-the-art technology is recognized for its capability of deep optical sectioning of living organs. It will enable USC investigators to perform ultra-sensitive, quantitative imaging of organ functions in health and disease with high spatial and temporal resolution, that other imaging modalities can not achieve. This critically needed instrument is essential to continue real core services which have been recently expanded due to the great success of the BISI. Janos Peti-Peterdi, the PI on this application, was recruited to USC in 2004 for his expertise in multi- photon imaging. In the past three years, Dr. Peti-Peterdi and his laboratory assisted a great number of HSC investigators to obtain preliminary data and images for grant proposals and scientific publications using his individually owned and maintained multi-photon microscope. This voluntary service, providing free access to, and supervised, assisted use of his own microscope was the basis of formally establishing the Multi-Photon Core. As the first step in transforming this function into a more robust, University wide resource, the BISI recently provided a full-time research associate for the core. This RA provides technical expertise to a growing number of investigators through BISI pilot projects. At the same time, Dr. Peti-Peterdi significantly expanded his own research so that his NIH, AHA-funded projects now require full capacity of his own microscope. There is clearly a critical need for a dedicated core equipment, and obtaining this shared instrument will be the final step of becoming a real Multi-Photon Core. As the PHS funded user base continues to expand, a lack of available multi-photon microscope time has become a major limiting factor in the utility of the core. The acquisition of the requested instrument will allow us to match resources of the core with the expanding demand for access to multi-photon in vivo organ microscopy, relieving the bottle neck that currently impedes scientific projects. Multi-photon microscopy of intact organs is an essential service provided by the core to many HSC investigators from the Departments of Medicine, Physiology, Cell and Neurobiology, Molecular Microbiology, and Immunology with existing, pending and renewal PHS grants. This multi-photon core is also critically needed for the USC Diabetes Research Center and the Clinical and Translational Science Institute, both being established pending PHS grants. [unreadable] [unreadable] [unreadable]